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Illicit or 'designer' benzodiazepines are a growing contributor to overdose deaths. We employed natural language processing (NLP) to study benzodiazepine mentions over 10 years on 270 online drug forums (subreddits) on Reddit. Using NLP, we automatically detected mentions of illicit and prescription benzodiazepines, including their misspellings and non-standard names, grouping relative mentions by quarter. On a collection of 17 861 755 posts between 2012 and 2021, we searched for 26 benzodiazepines (8 prescription; 18 illicit), detecting 173 275 mentions. The rate of posts about both prescription and illicit benzodiazepines increased consistently with increases in deaths involving both drug classes, illustrating the utility of surveillance via Reddit., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Herein, an electrochemical sensor based on samarium oxide anchored, reduced graphene oxide (Sm 2 O 3 /RGO) nanocomposite was developed for the rapid detection of carbendazim (CBZ). Different characterization methods were infused to deeply examine the morphology, composition, and elemental state of Sm 2 O 3 /RGO nanocomposite. The Sm 2 O 3 /RGO modified electrode exhibits an excellent electro-catalytic performance toward CBZ detection with a peak potential of +1.04 V in phosphate buffer solution (pH 3.0), which is superior to the RGO-, Sm 2 O 3 - and bare- electrodes. This remarkable activity can be credited to the synergetic effect generated by the robust interaction between Sm 2 O 3 and RGO, resulting in a well-enhanced electrochemical sensing ability. Impressively, the fabricated sensor shows improved electrochemical performance in terms of the wide working range, detection limit, and strong sensitivity. On a peculiar note, the electrochemical sensing performances of CBZ detection based on Sm 2 O 3 /RGO nanocomposite demonstrate an extraordinary behavior compared to the prior documented electro-catalyst. In addition, the fabricated Sm 2 O 3 /RGO sensor also displays good operational stability, reproducibility, and repeatability towards the detection of CBZ. Furthermore, it was successfully applied to the CBZ detection in food and environmental water samples with satisfactory recovery. In accordance with our research findings, the Sm 2 O 3 /RGO nanocomposite could be used as an electro-active material for effectual electrochemical sensing of food and environmental pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The indispensable usage of pesticides for the control and prevention of pests is probable and includes several types based on the problems in the crops. Among them, fungicides, are one problem-solving agent curing fungal developments. the disproportionate use of fungicides will lead to environmental deterioration and several health issues. The assessment of such fungicides is highly motivated to be detected. Under the class of two-dimensional materials, graphitic carbon nitride (GCN) with high surface area and high electrocatalytic activity was chosen as electrode material. The efficiency of GCN was improved with the subsequent substitution of selenium (Se) into the triazine ring as Se-GCN. The structural and surface analysis was done and the layered structure was proved. The electrochemical detection of CBM showed a lower detection limit at 6 nM with a linear range 0.099 μM-346.9 μM while, the absorption studies showed a LOD of 20 nM with a linear range of 0.099 μM-182.09 μM. The orange juice and vegetable extract samples had good recovery with CBM at Se-GCN modified disposable screen-printed electrode. The developed disposable electrode was more sensitive with 6.45 μAμM -1 cm 2 sensitivity and highly reactive with CBM. Moreover, the developed sensor will be more effective in sensing applications to avoid the menace generated by several agents., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Suicide is the second leading cause of death among youth ages 10-19 in the USA. While suicide has long been recognized as a multifactorial issue, there is limited understanding regarding the complexities linking adverse childhood experiences (ACEs) to suicide ideation, attempt, and fatality among youth. In this paper, we develop a map of these complex linkages to provide a decision support tool regarding key issues in policymaking and intervention design, such as identifying multiple feedback loops (e.g., involving intergenerational effects) or comprehensively examining the rippling effects of an intervention. We use the methodology of systems mapping to structure the complex interrelationships of suicide and ACEs based on the perceptions of fifteen subject matter experts. Specifically, systems mapping allows us to gain insight into the feedback loops and potential emergent properties of ACEs and youth suicide. We describe our methodology and the results of fifteen one-on-one interviews, which are transformed into individual maps that are then aggregated and simplified to produce our final causal map. Our map is the largest to date on ACEs and suicide among youth, totaling 361 concepts and 946 interrelationships. Using a previously developed open-source software to navigate the map, we are able to explore how trauma may be perpetuated through familial, social, and historical concepts. In particular, we identify connections and pathways between ACEs and youth suicide that have not been identified in prior research, and which are of particular interest for youth suicide prevention efforts., Competing Interests: Conflict of interest The authors declare that they have no competing interests.

Background: Despite recent rises in fatal overdoses involving multiple substances, there is a paucity of knowledge about stimulant co-use patterns among people who use opioids (PWUO) or people being treated with medications for opioid use disorder (PTMOUD). A better understanding of the timing and patterns in stimulant co-use among PWUO based on mentions of these substances on social media can help inform prevention programs, policy, and future research directions. This study examines stimulant co-mention trends among PWUO/PTMOUD on social media over multiple years., Methods: We collected publicly available data from 14 forums on Reddit (subreddits) that focused on prescription and illicit opioids, and medications for opioid use disorder (MOUD). Collected data ranged from 2011 to 2020, and we also collected timelines comprising past posts from a sample of Reddit users (Redditors) on these forums. We applied natural language processing to generate lexical variants of all included prescription and illicit opioids and stimulants and detect mentions of them on the chosen subreddits. Finally, we analyzed and described trends and patterns in co-mentions., Results: Posts collected for 13,812 Redditors showed that 12,306 (89.1%) mentioned at least 1 opioid, opioid-related medication, or stimulant. Analyses revealed that the number and proportion of Redditors mentioning both opioids and/or opioid-related medications and stimulants steadily increased over time. Relative rates of co-mentions by the same Redditor of heroin and methamphetamine, the substances most commonly co-mentioned, decreased in recent years, while co-mentions of both fentanyl and MOUD with methamphetamine increased., Conclusion: Our analyses reflect increasing mentions of stimulants, particularly methamphetamine, among PWUO/PTMOUD, which closely resembles the growth in overdose deaths involving both opioids and stimulants. These findings are consistent with recent reports suggesting increasing stimulant use among people receiving treatment for opioid use disorder. These data offer insights on emerging trends in the overdose epidemic and underscore the importance of scaling efforts to address co-occurring opioid and stimulant use including harm reduction and comprehensive healthcare access spanning mental-health services and substance use disorder treatment., (© 2022. The Author(s).)

Background: While reduced exposure to prescription opioids may decrease risks, including overdose and opioid use disorder, abrupt tapering or discontinuation may pose new risks., Objectives: To examine potentially unsafe tapering and discontinuation among dosage changes in opioid prescriptions dispensed to US patients on high-dose long-term opioid therapy., Design: Longitudinal observational study of adults (≥18 years) on stable high-dose (≥50 oral morphine milligram equivalents [MME] daily dosage) long-term opioid therapy during a 180-day baseline and a 360-day follow-up using all-payer pharmaceutical claims data, 2017-2019., Measures: Dosage tapering, increases, and/or stability during follow-up; sustained dosage stability, reductions, or discontinuation at the end of follow-up; and tapering rate. Patients could experience more than one outcome during follow-up., Results: Among 595,078 patients receiving high-dose long-term opioid therapy in the sample, 26.7% experienced sustained dosage reductions and 9.3% experienced discontinuation. Among patients experiencing tapering, 62.0% experienced maximum taper rates between > 10-40% reductions per month and 36.1% experienced monthly rates ≥ 40%. Among patients with mean baseline daily dosages ≥ 150 MME, 47.7% experienced a maximum taper rate ≥ 40% per month. Relative to baseline, 19.7% of patients experiencing tapering had long-term dosage reductions ≥ 40% per month at the end of follow-up., Implications: Dosage changes for patients on high-dose long-term opioid therapy may warrant special attention, particularly over shorter intervals, to understand how potentially sudden tapering and discontinuation can be reduced while emphasizing patient safety and shared decision-making. Rapid discontinuation of opioids can increase risk of adverse outcomes including opioid withdrawal., (Published by Elsevier B.V.)

Background: Timely data from official sources regarding the impact of the COVID-19 pandemic on people who use prescription and illegal opioids is lacking. We conducted a large-scale, natural language processing (NLP) analysis of conversations on opioid-related drug forums to better understand concerns among people who use opioids., Methods: In this retrospective observational study, we analyzed posts from 14 opioid-related forums on the social network Reddit. We applied NLP to identify frequently mentioned substances and phrases, and grouped the phrases manually based on their contents into three broad key themes: (i) prescription and/or illegal opioid use; (ii) substance use disorder treatment access and care; and (iii) withdrawal. Phrases that were unmappable to any particular theme were discarded. We computed the frequencies of substance and theme mentions, and quantified their volumes over time. We compared changes in post volumes by key themes and substances between pre-COVID-19 (1/1/2019-2/29/2020) and COVID-19 (3/1/2020-11/30/2020) periods., Results: Seventy-seven thousand six hundred fifty-two and 119,168 posts were collected for the pre-COVID-19 and COVID-19 periods, respectively. By theme, posts about treatment and access to care increased by 300%, from 0.631 to 2.526 per 1000 posts between the pre-COVID-19 and COVID-19 periods. Conversations about withdrawal increased by 812% between the same periods (0.026 to 0.235 per 1,000 posts). Posts about drug use did not increase (0.219 to 0.218 per 1,000 posts). By substance, among medications for opioid use disorder, methadone had the largest increase in conversations (20.751 to 56.313 per 1,000 posts; 171.4% increase). Among other medications, posts about diphenhydramine exhibited the largest increase (0.341 to 0.927 per 1,000 posts; 171.8% increase)., Conclusions: Conversations on opioid-related forums among people who use opioids revealed increased concerns about treatment and access to care along with withdrawal following the emergence of COVID-19. Greater attention to social media data may help inform timely responses to the needs of people who use opioids during COVID-19., (© 2022. The Author(s).)

Many pollinating insects exhibit flower constancy, i.e. they target flower species they have already experienced and fed from. While the insects might profit from reduced handling costs when revisiting similar flowers, flower constancy, in addition, is of benefit for the plants as it guarantees pollen transfer to conspecifics. Here we investigate whether the previous experience of an insect can also result in oviposition constancy, i.e. whether ovipositing on a given plant species will drive future oviposition preference in a female insect. We show that female hawkmoths (Manduca sexta), after having oviposited on a given plant species only once, indeed will prefer this plant in future oviposition choices. As oviposition preference is even affected 24 h after the moth has oviposited on a given plant, long term memory seems to be involved in this oviposition constancy. Our data furthermore suggest that, as shown for flower constancy, ovipositing moths increase their handling efficiency by targeting those host plants they have already experienced., (© 2021. The Author(s).)

Objective: To quantify discrepancies between opioid prescribing and dispensing via the percentage of patients with Electronic Medical Record (EMR) prescriptions who subsequently filled the prescription within 90 days, defined as congruence, and compared opioid congruence with related medications., Data Sources: Deidentified data from the IBM MarketScan Explorys Claims-EMR Dataset., Study Design: In this retrospective, observational study, we examined congruence for commonly prescribed controlled substances-opioids, stimulants, and benzodiazepines. Congruence was stratified by age group and sex., Data Collection/extraction Methods: Continuously enrolled adults aged 18-64 years with an EMR encounter (excluding inpatient settings) and ≥ 1 prescription for selected classes between 1/1/2016 and 10/2/2017., Principal Findings: During the study period, 1,353,478 adults had ≥1 EMR encounter. Patients with stimulants prescriptions had the highest congruence (83%) corresponding to 7151 claims for 8,635 EMR prescriptions, followed by opioids (66%; 62,766/95,690) and benzodiazepines (64%; 30,181/47,408). Chi-square testing showed congruence differed by age group within opioids (P < .0001) and benzodiazepines (P < .0001) and was higher among females within benzodiazepines (P < .0001)., Conclusions: These findings demonstrate that relying on claims data alone for opioid prescribing measures might underestimate actual prescribing magnitude by as much as one-third in these data. Combined EMR and claims data can help future research better understand characteristics associated with congruence or incongruence between prescribing and dispensing., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Suicide rates are steadily increasing among youth in the USA. Although several theories and frameworks of suicide have been developed, they do not account for some of the features that define suicide as a complex problem, such as a large number of interrelationships and cycles. In this paper, we create the first c omprehensive m ap o f a dverse c hildhood experiences (ACEs) and suicide for youth, by combining a participatory approach (involving 15 subject-matter experts) and network science. This results in a map of 946 edges and 361 concepts, in which we identify ACEs to be the most important factor (per degree centrality). The map is openly shared with the community to support further network analyses (e.g., decomposition into clusters). Similarly to the high-impact Foresight Map developed in the context of obesity, the largest map on suicide and ACEs to date presented in this paper can start a discussion at the crossroad of suicide research and network science, thus bringing new means to address a complex public health challenge.

Abstract: Results from preclinical sepsis studies using rodents are often criticized as not being reproducible in humans. Using a murine model, we previously reported that visceral adipose tissues (VAT) are highly active during the acute inflammatory response, serving as a major source of inflammatory and coagulant mediators. The purpose of this study was to determine whether these findings are recapitulated in patients with sepsis and to evaluate their clinical significance. VAT and plasma were obtained from patients undergoing intra-abdominal operations with noninflammatory conditions (control), local inflammation, or sepsis. In mesenteric and epiploic VAT, gene expression of pro-inflammatory (TNFα, IL-6, IL-1α, IL-1β) and pro-coagulant (PAI-1, PAI-2, TSP-1, TF) mediators was increased in sepsis compared with control and local inflammation groups. In the omentum, increased expression was limited to IL-1β, PAI-1, and PAI-2, showing a depot-specific regulation. Histological analyses showed little correlation between cellular infiltration and gene expression, indicating a resident source of these mediators. Notably, a strong correlation between PAI-1 expression in VAT and circulating protein levels was observed, both being positively associated with markers of acute kidney injury (AKI). In another cohort of septic patients stratified by incidence of AKI, circulating PAI-1 levels were higher in those with versus without AKI, thus extending these findings beyond intra-abdominal cases. This study is the first to translate upregulation of VAT mediators in sepsis from mouse to human. Collectively, the data suggest that development of AKI in septic patients is associated with high plasma levels of PAI-1, likely derived from resident cells within VAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

In this work, Ni-doped ZrO 2 nanoparticles (NPs) were used to decorate multi-walled carbon nanotubes (MWCNTs) to obtain a Ni-ZrO 2 /MWCNT nanocomposite, which acted as an efficient electrode material for the highly sensitive electrochemical detection of the anti-inflammatory drug 5-amino salicylic acid (5-ASA). The Ni-ZrO 2 NPs were obtained through a facile co-precipitation method, and the subsequent support of these Ni-ZrO 2 NPs onto MWCNTs was accomplished via an ultrasonication technique. Supporting Ni-ZrO 2 NPs on MWCNTs not only results in excellent catalytic properties, but it also substantially enhances the surface area, electrical conductivity, and electron transfer process. The electrochemical activity of the synthesized Ni-ZrO 2 /MWCNT nanocomposite was systematically investigated via cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The constructed Ni-ZrO 2 /MWCNT-modified glassy carbon (GC) electrode manifests superior electrocatalytic oxidation activity toward 5-ASA, with a lower peak potential compared with Ni-ZrO 2 -NP- and MWCNT-modified GC electrodes. Importantly, the proposed biosensor exhibited excellent sensitivity during the detection of 5-ASA with a wide linear concentration range (0.001-500 μM) and a low detection limit of 0.0029 μM. Moreover, the biosensor demonstrated excellent repeatability, reproducibility, stability, and high specificity toward 5-ASA detection in the presence of different interfering species. Furthermore, the biosensor showed satisfactory recovery rates in complex biological samples, such as human blood serum, human urine, and 5-ASA tablet samples.

Rickettsia are obligate intracellular pathogens transmitted by arthropod vectors. The re-emergence of several rickettsioses imposes severe global health burden. In addition to the well-established rickettsial pathogens, newer rickettsial species and their pathogenic potentials are being uncovered. There are many reports of spotted and typhus fever caused by rickettsiae in India. Hence, in this study we screened the ectoparasites of pet and domestic animals for the presence of rickettsia using polymerase chain reaction. Nine cat flea samples (Ctenocephalides felis felis), that tested positive for the presence of rickettsia were subjected to Multi Locus Sequence Typing. Nucleotide sequencing and Phylogenetic analysis of gltA, ompB and 16rrs genes revealed that the rickettsiae detected in cat fleas was Rickettsia asembonensis. Further studies are required to assess Rickettsia asembonensis pathogenic potential to human and its enzootic maintenance of in various hosts and vectors., (© 2020 The Royal Entomological Society.)

Introduction: U.S. hospital discharges for opioid overdose increased substantially during the past two decades. This brief report describes 90-day readmissions among patients discharged from inpatient stays for opioid overdose., Methods: In 2018, survey-weighted analysis of hospital stays in the 2016 Healthcare Cost and Utilization Project National Readmissions Database yielded the national estimated proportion of patients with opioid overdose stays that had all-cause readmissions within ≤90 days. A multivariable logistic regression model assessed index stay factors associated with readmission by type (opioid overdose or not). Number of readmissions per patient was assessed., Results: More than 24% (n=14,351/58,850) of patients with non-fatal index stays for opioid overdose had at least one all-cause readmission ≤90 days of index stay discharge and 3% (n=1,658/58,850) of patients had at least one opioid overdose readmission. Less than 0.2% (n=104/58,850) of patients had more than one readmission for opioid overdose. Patient demographic characteristics (e.g., male, older age), comorbidities diagnosed during the index stay (e.g., drug use disorder, chronic pulmonary disease, psychoses), and other index stay factors (Medicare or Medicaid primary payer, discharge against medical advice) were significantly associated with both opioid overdose and non-opioid overdose readmissions. Nearly 30% of index stays for opioid overdose included heroin, which was significantly associated with opioid overdose readmissions., Conclusions: A quarter of opioid overdose patients have ≤90 days all-cause readmissions, although opioid overdose readmission is uncommon. Effective strategies to reduce readmissions will address substance use disorder as well as comorbid physical and mental health conditions., (Published by Elsevier Inc.)

Objective: Despite recent decreases in opioid prescribing rates, evidence suggests there is substantial variation in the way opioids are prescribed by providers. This study aims to identify patterns in high-volume opioid prescribing., Methods: We conducted partitioning-around-medoids cluster analysis using the IQVIA Prescriber Profile dataset, including the number of opioid prescriptions filled at US retail pharmacies aggregated at the prescriber-level from July 2016 through June 2017. Clustering was used to identify prescription patterns within a sample of 10,000 high-volume opioid prescribers (defined as the top 10% of prescribers by number of opioid prescriptions during the 12-month period). Clustering variables included prescription counts by opioid type, and prescriber specialty, age, and region., Results: Family medicine (32%), internal medicine (23%), and orthopedics (11%) were the most common high-volume prescribing specialties. Across specialties, hydrocodone and oxycodone were the most-frequently prescribed opioid types. Thirty-five clusters of prescribers were obtained, consistently comprised of a single majority specialty and region. All majority high-prescribing specialties were represented in Southern clusters, indicating consistently high volume opioid prescribing across specialties in the region. Prescribing patterns varied by drug type and region - across every Northeastern cluster, oxycodone prescribing was higher than hydrocodone. While clusters of pain medicine specialists had the highest median total prescriptions, emergency medicine specialist clusters had some of the lowest., Conclusions: These results provide a clearer picture of current patterns among high-volume prescribers, who accounted for almost two-thirds of all opioid prescriptions. In light of the ongoing opioid overdose epidemic, this knowledge is critical for prevention activities., (Published by Elsevier B.V.)

In the US, one in four adults has two or more chronic conditions; this population accounts for two thirds of healthcare spending. Comorbidity, the presence of multiple simultaneous health conditions in an individual, is increasing in prevalence and has been shown to impact patient outcomes negatively. Comorbidities associated with diabetes are correlated with increased incidence of preventable hospitalizations, longer lengths of stay (LOS), and higher costs. This study focuses on sex and race disparities in outcomes for hospitalized adult patients with and without diabetes. The objective is to characterize the impact of comorbidity burden, measured as the Charlson Weighted Index of Comorbidities (WIC), on outcomes including LOS, total charges, and disposition (specifically, probability of routine discharge home). Data from the National Inpatient Sample (2006-2011) were used to build a cluster-analytic framework which integrates cluster analysis with multivariate and logistic regression methods, for several goals: (i) to evaluate impact of these covariates on outcomes; (ii) to identify the most important comorbidities in the hospitalized population; and (iii) to create a simplified WIC score. Results showed that, although hospitalized women had better outcomes than men, the impact of diabetes was worse for women. Also, non-White patients had longer lengths of stay and higher total charges. Furthermore, the simplified WIC performed equivalently in the generalized linear models predicting standardized total charges and LOS, suggesting that this new score can sufficiently capture the important variability in the data. Our findings underscore the need to evaluate the differential impact of diabetes on physiology and treatment in women and in minorities.

Aims: In addition to providing external quality assessment (EQA) schemes, United Kingdom National External Quality Assessment service (UK NEQAS) for Molecular Genetics also supports the education of laboratories. As an enhancement to the Molecular Pathology EQA scheme, a human cell-line reference sample, manufactured by Thermo Fisher Scientific (AcroMetrix), was provided for analysis. This contained many variants, present at frequencies between 1% and 17.9%., Methods: One hundred and one laboratories submitted results, with a total of 2889 test results on 53 genes being reported. Known polymorphisms, 46/2889 (1.59%) results, were excluded. Variants detected in the seven most commonly reported (and clinically relevant) genes, KRAS, NRAS, BRAF, EGFR, PIK3CA, KIT and PDGFRA , are reported here, as these genes fall within the scope of UK NEQAS EQA schemes., Results: Next generation sequencing (NGS) was the most commonly performed testing platform. There were between 5 and 27 validated variants in the seven genes reported here. Eight laboratories correctly reported all five NRAS variants, and two correctly reported all eight BRAF variants. The validated mean variant frequency was lower than that determined by participating laboratories, with single-gene testing methodologies showing less variation in estimated frequencies than NGS platforms. Laboratories were more likely to correctly identify clinically relevant variants., Conclusions: Over 100 laboratories took the opportunity to test the 'educational reference sample', showing a willingness to further validate their testing platforms. While it was encouraging to see that the most widely reported variants were those which should be included in routine testing panels, reporting of variants was potentially open to interpretation, thus clarity is still required on whether laboratories selectively reported variants, by either clinical relevance or variant frequency., Competing Interests: Competing interests: NN, MB, AL and KLN were employed by Thermo Fisher Scientific. Other authors have no competing interest to declare., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Lysozyme is an important component of the host innate defense system. It cleaves the β-1,4 glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine of bacterial peptidoglycan and induce bacterial lysis. Staphylococcus aureus (S. aureus), an opportunistic commensal pathogen, is highly resistant to lysozyme, because of the O-acetylation of peptidoglycan by O-acetyl transferase (oatA). To understand the structure-function relationship of lysozyme resistance in S. aureus by peptidoglycan O-acetylation, we adapted an integrated approach to (i) understand the effect of lysozyme on the growth of S. aureus parental and the oatA mutant strain, (ii) study the lysozyme induced lysis of exponentially grown and stationary phase of both the S. aureus parental and oatA mutant strain, (iii) investigate the dynamic interaction mechanism between normal (de-O-acetylated) and O-acetylated peptidoglycan substrate in complex with lysozyme using molecular docking and molecular dynamics simulations, and (iv) quantify lysozyme resistance of S. aureus parental and the oatA mutant in different human biological fluids. The results indicated for the first time that the active site cleft of lysozyme binding with O-acetylated peptidoglycan in S. aureus was sterically hindered and the structural stability was higher for the lysozyme in complex with normal peptidoglycan. This could have conferred reduced survival of the S. aureus oatA mutant in different human biological fluids. Consistent with this computational analysis, the experimental data confirmed decrease in the growth, lysozyme induced lysis, and lysozyme resistance, due to peptidoglycan O-acetylation in S. aureus.

Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of > 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

Assays for initiating, controlling and studying endothelial cell behavior and blood vessel formation have applications in developmental biology, cancer and tissue engineering. In vitro vasculogenesis models typically combine complex three-dimensional gels of extracellular matrix proteins with other stimuli like growth factor supplements. Biomaterials with unique micro- and nanoscale features may provide simpler substrates to study endothelial cell morphogenesis. In this work, patterns of nanoporous, nanothin silicon membranes (porous nanocrystalline silicon, or pnc-Si) are fabricated to control the permeability of an endothelial cell culture substrate. Permeability on the basal surface of primary and immortalized endothelial cells causes vacuole formation and endothelial organization into capillary-like structures. This phenomenon is repeatable, robust and controlled entirely by patterns of free-standing, highly permeable pnc-Si membranes. Pnc-Si is a new biomaterial with precisely defined micro- and nanoscale features that can be used as a unique in vitro platform to study endothelial cell behavior and vasculogenesis., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Staphylococcus aureus is one of the major causes of skin and soft tissue infections. In this study we compared the antimicrobial activity of two different TiO2 nanoformulations against Staphylococcus aureus. We synthesized TiO2 nanoparticles of approximately 80 nm diameter and TiO2 nanowires of approximately 100 nm diameter. Both nanoformulations possess anti-microbial activity; were non-hemolytic and cytocompatible. However, the anti-staphylococcal activity of TiO2 nanowires was better than the nanoparticles. In broth culture, growth of S. aureus was only partially inhibited by 2% and 4 wt% TiO2 nanoparticles and completely inhibited by TiO2 nanowires till 24 h. TiO2 nanowires treated S. aureus cells exhibits diminished membrane potential than nanoparticle treated cells. The anti-microbial properties of both TiO2 nanoformulations were validated using ex vivo porcine skin model which supplements the in vitro assays. Anti-bacterial activity of the TiO2 nanowires were also validated against multi drug resistant pathogenic strains of S. aureus, showing the clinical potency of the TiO2 nanowires compared to its nanoparticles.